In this paper we develop a forecasting algorithm for recurrent patterns in consumer demand. We study this problem in two different settings: pull and push models. We discuss several features of the algorithm concerning sampling, periodic approximation, denoising and forecasting.

Abstract: Down Syndrome (DS) is a common genetic disorder characterized by an extra copy of chromosome 21, leading to dysregulation of various metabolic pathways. Oxidative stress in DS is associated with neurodevelopmental defects, neuronal dysfunction, and the onset of dementia re-sembling Alzheimer's disease. Additionally, chronic oxidative stress contributes to cardiovascular diseases and certain cancers prevalent in DS individuals. This study investigates the impact of ageing on oxidative stress and liver fibrosis using a DS murine model (Ts2Cje mice). The liver in DS mice shows increased oxidative stress and impaired antioxidant defenses, as evidenced by reduced glutathione levels and increased lipid peroxidation. Furthermore, DS liver exhibits an altered in-flammatory response as measured by the expression of cytokines and heat shock proteins. DS liver also displays dysregulated lipid metabolism, indicated by altered expression of peroxisome prolif-erator-activated receptors and fatty acid transport proteins. Consistently, these changes might contribute to non-alcoholic fatty liver disease development, a condition characterized by liver fat accumulation. Finally, histological analysis of DS liver reveals increased fibrosis and steatosis, in-dicative of potential progression to liver cirrhosis. This finding highlights the increased risk of liver pathologies in DS individuals, particularly when combined with the higher prevalence of obesity and metabolic dysfunctions in DS patients. These results shed light on the liver's role in DS-associated pathologies and suggest potential therapeutic strategies targeting oxidative stress and lipid metabolism to prevent or mitigate liver-related complications in DS individuals.

Monitoring the quality of stored bulk grain is generally done using temperature cables hung from silo roofs. Little investigation has been done into the effects of number of sensors and their placement in terms of reliability of the monitoring system with regard to making stored grain quality management decisions. A previously developed 3D finite element simulation model was verified and used to investigate these aspects. In the first study, a silo was loaded with about 228.6 Mg (9000 bushels) of maize and six temperature cables were placed in the grain mass. The maize was aerated continuously for a period of two weeks, and the cable sensor temperatures were compared to the predicted temperatures which were in close agreement with the observed readings. The standard error of prediction ranged from 2.0 to 3.7°C. In the second study, 15 and 30 sensors were placed at manufacturer recommended depths and horizontal locations in the grain mass of three silo sizes (i.e., 11x11, 14.6x14.6 and 14.6x18.3 m diameter by eave height). The average grain temperatures predicted by the 15 and 30 sensors over a one-year simulation period were compared to the average grain temperatures predicted for the entire grain mass (1968, 3052, and 3204 mesh nodes). The number of sensors needed to monitor stored grain temperatures reliably in the three silo sizes investigated heavily depended on whether the aeration control strategy achieved a sufficiently low temperature by the time the aeration fans were turned off and sealed ahead of the non-aerated storage period. Fifteen or 30 sensors were sufficient to monitor grain temperatures during the aeration cooling period but for the two larger silo sizes more than 30 sensors would be needed during the storage period. As silo size increased, and surface-to-volume ratio decreased, grain temperatures remained lower during the storage period. Results support the best management practice recommendation of leaving cooled grain cold and not warming it up in the spring ahead of storage into the summer.

People with Down syndrome present cognitive difficulties that affect their reading skills. In this study we present results about the use of gestural interaction with Kinect sensor to improve the reading skills of students with Down syndrome. Following a case of study method for small samples with disabilities, measuring different variables related to reading skills in an experimental group and in a control group. We found improvements in the visual association, visual comprehension, sequential memory, and visual integration after this stimulation in the experimental group compared to the control group. Also, we found that the number of error and delay time of interaction decrease between sessions in the experimental group.

Crosslinking of proteins for their irreversible immobilization on surfaces is a proven and popular method. However, many protocols lead to random orientation and the formation of undefined or even inactive by-products. Most concepts to obtain a more targeted conjugation or immobilization requires the recombinant modification of at least one binding partner, which is often impractical or prohibitively expensive. Here a novel method is presented, which is based on the chemical preactivation of Protein A or G with selected conventional crosslinkers. In a second step, the antibody is added, which is subsequently crosslinked in the Fc part. This leads to an oriented and covalent immobilization of the immunoglobulin with a very high yield. Protocols for Protein A and Protein G with murine and human IgG are presented. This method may be useful for the preparation of columns for affinity chromatography, immunoprecipitation, antibodies conjugated to magnetic particles, permanent and oriented immobilization of antibodies in biosensor systems, microarrays, microtitration plates or any other system, where the loss of antibodies needs to be avoided, and maximum binding capacity is desired. This method is directly applicable even to antibodies in crude cell culture supernatants, raw sera or protein-stabilized antibody preparations without any purification nor enrichment of the IgG. This new method delivered much higher signals as a traditional method and, hence, seems to be preferable in many applications.

The acquisition of regional, 1 metre resolution LIDAR in the PNG Highlands combined with 3D modelling in MoveTM has revolutionized our understanding of the evolution of the Porgera gold mine and areas of new potential. The new 3D model demonstrates active pull-apart basins along a regional transfer during ongoing fold and thrust deformation. When overlain on regional aeromagnetic data, new potential is revealed. The Porgera gold mine is one of the richest in the world and lies in a wide valley at an elevation of 2800m surrounded by mountains up to 4000m high in the middle of the PNG Highlands. It lies along a major lineament, the Porgera Transfer Zone (PTZ), cutting across the orogen that is associated with a 50 km offset of the ophiolite belt. To the NW of the mine there is an extensive belt of low- to high-grade metasediments that formed in deep water during Jurassic rifting, but were metamorphosed during Eocene subduction to the north. Subduction ceased due to accretion of the Sepik Terrane which caused inversion and mild erosion of the Porgera area. The Late Oligocene onset of wrenching in the Mobile Belt to the north placed that area into extension, emplacing metamorphic core complexes, and led to regional subsidence in the Early Miocene. Collision of the margin with the Melanesian Arc in the Middle Miocene caused Late Miocene to Pliocene orogenesis creating the broad mountain belt that we see today, that is still active, as shown by the 2018 MW 7.5 earthquake. Regional mapping of the area using high resolution LIDAR in association with limited field mapping, analysis of gravity and magnetics data and drilling of 300-500m deep core-holes has allowed development of a detailed 3D structural model. The Porgera valley is constrained laterally by the Eastern Boundary and Western Boundary dextral strike-slip faults that lie along the PTZ cutting across the orogeny. However, whilst the position and nature of the faults is clear, due to bending, fracturing and offset of major synclines and anticlines, the faults do not crop-out as significant through-going features. Rather, the dextral offset of basement is soft-linked to the Tertiary limestones at surface due to intervening thick, ductile Cretaceous shales. Fold and thrust structures are ubiquitous in the Tertiary limestones, but the youngest structural features are large extensional faults, particularly around the Porgera valley. The intrusive underlying the Porgera ore-body was emplaced at 6.0+-0.3 Ma, the time of maximum compression during orogenesis. At this time the Eastern Boundary fault and Western Boundary fault were both active allowing a pull-apart basin to form locally along the PTZ at the south-eastern boundary of the Jurassic metasediments. This enabled emplacement of the intrusive. The gold-bearing fluids from the intrusive and metasediments were brought up through the Mesozoic muds to the contact with the Paleogene carbonates where the Porgera ore body was emplaced.

Stemborer pests contribute to significant maize crop yield loses incurred by the smallholder famers in Ethiopia. The problem requires requires concerted effort to learn and adopt new innovations to find a long lasting solution. In this study, the on-farm implementation of the push-pull technology (PPT) was used as a platform for interaction and enhancing the social learning among the stakeholders in the maize growing Woredas of Bako Tibe, Jimma Arjo and Yayu in the Oromia region. The main stakeholders were the smallholder maize farmers, researchers and the extension staffs. The study took place between August 2014 to May 2015. The PPT is a biological based strategy addresses the stemborer pest problem in maize crop. Under the strategy, maize crop is intercropped with a stemborer moth repellent fodder legume, Desmodium (the push) together with an attractant trap plant, Napier/Brachiaria grass (the pull) planted around maize-legume intercrop. The study was implemented based on the transdisciplinary action research approach and qualitative data collected during focus group discussions, key informant interviews, stakeholder workshops, participant observations and on-farm PPT demonstrations. The findings show that, the involvement of different stakeholders in joint PPT activities in an interactive environment is an innovation in itself. It creates opportunities for the stakeholders’ empowerment as well as deliberating on the contributions from each other to overcome uncertainties about the technology and create new knowledge. The intercropping strategy of maize with Desmodium and Napier/Brachiaria is used to reintroduce the traditional mixed cropping system of smallholder agriculture as strategy for control of pests.

Transdisciplinary research approach requires that different scientists with their discipline-specific theories, concepts and methods find ways to work together with other societal players to solve a real-life problem. In order to put this into practice, Trans-disciplinary Action Research (TDR) approach was applied in this study using Push pull technology (PPT) as a boundary object. The study was conducted in Bako Tibe, Jimma arjo and Yayu Woredas (Districts) in the Oromia region of Ethiopia from August 2014 to April 2015. PPT is a biological based mechanism developed by researchers for stemborer pest control in maize. It involves inter-cropping maize with a stemborer moth-repellent silverleaf or Greenleaf Desmodium (push), and planting an attractive trap crop, Napier or Brachiaria grass (pull), around the maize crop. On farm PPT implementation was used to provide an opportunity for collaboration, interaction and learning among heterogeneous set of stakeholders comprising of researchers from Ethiopian Institute of Agricultural research and the practitioners from the ministry of agriculture and smallholder farmers/traders. The data was collected using mixed methods approach comprising of key informant interviews, Focus Group discussions, workshops, on-farm practical demonstrations and participant observations. The findings shows that; collaborative leadership provides a chance for the stakeholders to participate in the technology learning and decision making by enabling them to jointly contribute skills towards development, refinement and adaptation of PPT. In situations where there are conflicts, they are embraced and become opportunities for in-depth learning, finding solutions and adaptation rather than being sources of contradictions or misunderstandings. Leadership roles taken by farmers play a key role in terms of ability to reflect on their own practices and drawing on scientific explanations from researchers. It also enables them take lead in new technology implementation and information sharing in free and easy manner with fellow farmers and other stakeholders. Although PPT perennial nature of cropping provides opportunities for continuous stakeholder interaction and learning, it requires a personally committed leadership and formal institutional engagements for the sustainability of its activities spanning over several cropping seasons. Market forces and the involvement of private sector players also has a role to achieve this as shown from the involvement of individual farmers and traders in Desmodium and Brachiaria seed production, collection and distribution.

In this work, the apparent shear strength at the interface between a bamboo fiber and the surrounding poly(lactic acid) (PLA) matrix is quantified. A method for processing pull-out test samples within a controlled embedded length is proposed and the details of the test procedure are presented, along with a critical discussion of the results. Two series of samples are considered: untreated and mercerized bamboo fibers from the same batch, embedded in the same polyester matrix. Electron and optical microscopy are used to observe the fiber-matrix interface before and after the test, and to identify the failure mode of each sample, especially as regards the occurrence of fibrillation in the fiber bundles. The values of apparent interfacial shear strength are calculated only for regular fibers successfully pulled out from the matrix, and reported with their statistical variations. Mercerization, whose efficiency was proven by Fourier Transform InfraRed (FTIR) spectroscopy, did not appear though to improve the quality of the interface (τ_app = 7.0 ± 3.1 MPa for untreated fibers and τ_app = 5.3 ± 2.4 MPa for treated fibers).

We have recently presented a unified quantum gravity theory [1]. Here we extend on that work and present an even simpler version of that theory. For about hundred years, modern physics has not been able to build a bridge between quantum mechanics and gravity. However, a solution may be found here; we present our quantum gravity theory, which is rooted in indivisible particles where matter and gravity are related to collisions and can be described by collision space-time. In this paper, we also show that we can formulate a quantum wave equation rooted in collision space-time, which is equivalent to mass and energy.The beauty of our theory is that most of the main equations that currently exist in physics are not changed (in terms of predictions), except at the Planck scale. The Planck scale is directly linked to gravity and gravity is, surprisingly, actually a Lorentz symmetry as well as a form of Heisenberg uncertainty break down at the Planck scale. Our theory gives a dramatic simplification of many physics formulas without altering the output predictions. The relativistic wave equation, the relativistic energy momentum relation, and Minkowski space can all be represented by simpler equations when we understand mass at a deeper level. This not attained at a cost, but rather a reflection of the benefit in having gravity and electromagnetism unified under the same theory.

in this work formulations of "environmentally compatible" silicone-based antifouling synthesized in the laboratory and based on copper and silver on silica/titania oxides have been characterized, capable of replacing the non-ecological antifouling paints currently on the market. The texture properties and the morphological analysis of these powders with an antifouling action indicate that their activity is linked to the nanometric size of the particles and to the homogeneous dispersion of the metal on the substrate. The presence of two metal species on the same support limits the for-mation of nanometric species and therefore the formation of homogeneous compounds. The presence of the antifouling filler (specifically the one based on TiO2 and Ag) facilitates the achievement of a higher degree of cross-linking of the pure resin, and therefore a better compactness and completeness of the coating. This leads to a consequent better degree of adhesion to the tie-coat and therefore to the steel support used for the construction of the boats.

In this review we extensively describe the main post-translational modifications that give rise to the multiple proteoforms characterized to date in the human salivary proteome and their potential role. Most of the data reported were obtained by our group in over twenty-five years of research carried out on human saliva mainly by applying a top-down strategy. At the beginning we describe the products generated by proteolytic cleavages, which can occur before and after secretion. In this section the most relevant families of salivary proteins are also described. Next, we report the current information concerning the human salivary phospho-proteome and the limited news available on sulfo-proteome. Three sections are dedicated to the description of the glycation and enzymatic glycosylation. Citrullination and N- and C- terminal PTMs and a miscellaneous of other modifications are described in the last two sections. Results highlighting the variation in the level of some proteoforms in local or systemic pathologies are also reviewed along the sections of manuscript to underline the impact and relevance of this information for the development of new diagnostic biomarkers useful in clinical practice.

Down syndrome (DS) is a leading human genomic abnormality resulting from the trisomy of chromosome 21. The genomic base of the aneuploidy behind this disease is complex, and this complexity poses formidable challenges to understanding the underlying molecular basis. In the spectrum of the classic DS risk factor associations the role of nutrients, vitamins, and in general, the foodborne associated background as part of the events leading ultimately to chromosome nondisjunction has long been recognized as a well-established clinical association. The integrity of the microbiome is a basic condition in these events, and the dysbiosis may be associated with secondary health outcomes, the possible association of DS development with maternal gut microbiota should require more attention. We have hypothesized that different classes of antibiotics might promote or inhibit the proliferation of different microbial taxa and hence, we might find associations between the use of different classes of antibiotics and the prevalence of DS through the modification of the microbiome. As antibiotics are considered major disruptors of the microbiome, it could be hypothesized that the consumption/exposure of certain classes of antibiotics might be associated with the prevalence of DS in European countries (N=30). Utilizing three different statistical methods, comparisons have been made between the average yearly antibiotic consumption (1997-2020) and the prevalence of people living with DS estimated for 2019 as a percentage of the population in European countries. We have found strong statistical correlations between the consumption of tetracycline (J01A) and the narrow-spectrum, beta-lactamase-resistant penicillin (J01CF) and the prevalence of DS.

This paper aims to determine the insecticidal activity of Panyawan (Tinospora rumphii) leaf extract against American cockroach (Periplaneta americana). A quantitative experimental research design was employed in the study. Cockroach strains were collected through trapping and hand catch methods. Panyawan leaf was collected and extracted to achieve seven different concentrations. The concentrations and controls were tested against the strains through the standard contact glass jar bioassay. Results revealed that the shortest knock-down time was achieved by the positive control at 1.08 minutes while the Extracts of Panyawan leaf reported a 1.42 to 20.25 minutes knock-down time. Probit Regression reported that the lethal concentration 50 of Panyawan leaf extract was 15.836%. One-Way ANOVA revealed that there is a significant difference in the knock-down times of cockroaches when exposed to different Panyawan leaf extract concentrations, negative and positive controls (p<0.01). Homogeneous subsets derived from Post Hoc Test using Tukey’s Honest Significant Difference reported that there is no significant difference between positive control and Extract 100% (p>0.01).

Failure of wind turbines is a multi-faceted problem and its monetary impact is often unpredicted. In this study, we present a novel application of survival analysis on wind turbine reliability performance that includes accounting of previous failures and history of scheduled maintenance. We investigate the operational, climatic and geographical factors which affect wind turbine failures and model the risk rate of wind turbine failures based on data from 109 turbines in Germany operating during a period of 19 years. Our analysis showed that adequately scheduled maintenance can increase the survivorship of wind turbine systems and electric subsystems up to 2.8 and 3.8 times, respectively compared to the ones without scheduled maintenance. Geared-drive wind turbines and their electrical systems were observed to have 1.2- and 1.4-times higher survivorship, respectively, compared to direct-drive turbines and their electrical systems. It is also found that survivorship of frequently-failed wind turbine components, such as switches, is worse in geared-drive than in direct-drive wind turbines. We show that survival analysis is a useful tool for guiding the reduction of operating and maintenance costs of wind turbines.

Individual users' payment behaviors have changed. The diffusion of mobile devices makes people suitable for proximity mobile payment (PMP) services without the need for traditional payment. Existing mobile payment literature mainly focuses on users' adoption and continuous usage behavior, nevertheless, switching behavior on payment received little attention, especially focusing on why users switch from traditional payment to PMP. Thus, the objective of the current research is to investigate factors influencing users’ traditional payment - PMP switching to comprehend how these factors shape users’ switching intentions. We developed a traditional payment - PMP transition model based on the push-pull-mooring framework derived from migration theory. This research adopted a structural equation modeling analysis on 311 valid data. The findings indicate that a push factor drives users away from traditional payment in terms of dissatisfaction. The pull factors, including perceived substitutability and perceived usefulness, attract users to PMP. Furthermore, in terms of perceived technical compatibility, a positive mooring factor facilitates users' switching to PMP. The negative mooring factor, in terms of perceived risk, hinder users' switching intention. However, another pull factor - perceived ease of use, failed to influence switching intention significantly. This study found some distinctions between mobile payment switching and mobile payment adoption. These findings provide pivotal insights for mobile payment service providers.

Background: Down Syndrome is the most well-studied aneuploidy condition in humans. It is associated with multiple disease phenotypes including cardiovascular, neurological, haemato-logical, and immunological disease processes. In this review paper we aim to discuss the research into gene expression studies performed at the fetal stage of development. Methods: A descriptive review was performed including all papers published on the PubMed database between Septem-ber 1960- September 2022. Results: In the amniotic fluid, genes such as COL6A1 and DSCR1 are affected, causing the phenotypical craniofacial changes. Other genes affected in amniotic fluid in-cluding: GSTT1, CLIC6, ITGB2, C21orf67, C21orf86 and RUNX1. In the placenta, MEST, SNF1LK and LOX were dysregulated, affecting nervous system development. In the brain DYRK1A, DNMT3L, DNMT3B, TBX1, olig2 and AQP4 were found to be dysregulated, affecting the nervous system and intellectual disability. In the cardiac tissues GART, EST2 and ERG found to be dysregulated causing secondary heart field abnormalities. XIST, RUNX1, SON, ERG and STAT1 dysregulated causing myeloproliferative disorders. Conclusions: Differential expression of genes provides clues to the genetic consequences of DS. A better understanding of these processes could eventually to lead to the development of genetic and pharmacological therapies.

People with Down syndrome have more visual problems than general population. They experience a premature aging, and it would be expected they will also have an acceleration in worsening visual function. A prospective observational study which includes visual acuity, refractive error, accommodation, binocular and colour vision was performed to young adults with (n=69) and without (n=65) Down syndrome and to a senior group (n=55) without Down syndrome. Results showed significant differences in visual acuity between groups (p&lt;0.001) and it can be improved with a new prescription in 40% of the participants with Down syndrome. Regarding to accommodative state, no significant differences were found between groups of young people. Concerning binocular vision, 64.7% of strabismus was observed in the group with Down syndrome (p&lt;0.001). Visual abnormalities are significant in young adults with Down syndrome and are different from those of older people without Down syndrome, some of which can be improved by providing the optimal prescription as well as regular eye examinations.

In this work, we compiled our research on lanthanide-based luminescent materials, prepared down-shifter layers, and studied their effect on photovoltaic (PV) mini-modules. The compounds we have prepared (C1-C17), with formulas [Eu2(phen)2(bz)6] (C1), [Eu2(bphen)2(bz)6] (C2), [Eu(tta)3bphen] (C3), [Eu(bta)3pyz-phen] (C4), [Eu(tta)3pyz-phen] (C5), [Eu(bta)3me-phen] (C6), [Er(bta)3me-phen] (C7), [Yb(bta)3me-phen] (C8), [Gd(bta)3me-phen] (C9), [Yb(bta)3pyz-phen] (C10), [Er(tta)3pyz-phen] (C11), [Eu2(bz)4(tta)2(phen)2] (C12), [Gd2(bz)4(tta)2(phen)2] (C13), [EuTb(bz)4(tta)2(phen)2] (C14), [EuGd(bz)4(tta)2(phen)2] (C15), [Eu1.2Gd0.8(bz)4(tta)2(phen)2] (C16) and [Eu1.6Gd0.4(bz)4(tta)2(phen)2] (C17), can be grouped into three families based on their composition: Series C1–6 were synthesized using Eu3+ ions and phenanthroline derivatives as the neutral ligands, and fluorinated β-diketonates as the anionic ligands. Complexes C7–11 were prepared with ligands similar to those of compounds C1–6 but were synthesized with Er3+, Yb3+, or Gd3+ ions. Series C12–17 exhibit the general formula [M1M2(bz)4(tta)2(phen)2], where M1 and M2 can be Eu3+, Gd3+, or Tb3+ ions, and the ligands are benzoate (bz–), 2-thenoyltrifluoroacetone (tta–) and 1,10–phenanthroline (phen). All compounds were characterized using X-ray techniques, and their photoluminescent properties were studied. We then examined their impact on the EQE (External Quantum Efficiency) of PV mini-modules and their durability in a climate chamber when embedded in PMMA and EVA films. This review emphasizes the methodology employed and the key findings, including enhanced mini-module efficiency. Additionally, we present promising results on the application of compound C6 in a bifacial solar cell.

Wildlife conservation is an important component of environmental sustainability and can be improved by reviewing the performance of its three major models – common pool, top-down regulatory, and private resource -- under varying environmental and socioeconomic conditions. Generally, the private resource model is the most sustainable because it provides the best incentives to balance the needs of humans and wildlife, to maintain general wildlife habitat, and to adapt quickly to changing environmental and/or socioeconomic conditions. Top-down or “command and control” regulation, however, can be employed as a model of last resort if the private resource model shows signs of failing to protect specific species from local extirpation or extinction, which it is most likely to do for migratory species, species with close commercial substitutes, and species with no direct commercial value. Top-down regulators may also be needed to enforce property rights arrangements like catch shares and to monitor resources that remain in the common pool in the event that socioeconomic or environmental conditions change sufficiently to trigger the tragedy of the commons.

Protein translational modifications (PTMs) generate an enormous, but as yet undetermined, expansion of the expressed proteoforms. In this Viewpoint, we firstly differentiate the concepts of proteoform and peptidoform by reviewing and discussing previous literature. We show that the current PTM biological investigation and annotation largely follow a PTM site-specific rather than proteoform-specific approach. We further illustrate a potentially useful matching strategy in which a particular “modified peptidoform” is matched to the corresponding “unmodified peptidoform” as a reference for the quantitative analysis between samples and conditions. We suggest this strategy could provide directly relevant information for learning the PTM site-specific biological functions. Accordingly, we advocate for the wider use of the nomenclature “peptidoform” in the future bottom-up proteomic studies.

Neurodevelopmental disorders arise from genetic and/or from environmental factors and are characterized by different degrees of intellectual disability. The mechanisms that govern important processes sustaining learning and memory, which are severely affected in intellectual disability, have classically been thought to be exclusively under neuronal control. However, this vision has recently evolved into a more integrative conception, in which astroglia, rather than just acting as metabolic supply and structural anchoring for neurons, interact at distinct levels modulating neuronal communication and possibly also cognitive processes. Recently, genetic tools have made it possible to specifically manipulate astrocyte activity unraveling novel functions that involve astrocytes in memory function in the healthy brain. However, astrocyte manipulation has also underscored potential mechanisms by which dysfunctional astrocytes could contribute to memory deficits in several neurodevelopmental disorders revealing new pathogenic mechanisms in intellectual disability. Here, we review the current knowledge about astrocyte dysfunction that might contribute to learning and memory impairment in neurodevelopmental disorders, with special focus on Fragile X syndrome and Down syndrome.

Recent progress in the fabricating flexible electronics has been developed significantly due to the increased interest of the flexible electronics which can be applied to enormous fields not only to conventional electronic devices but to bio/eco electronic devices. Flexible electronics can be applied to wide range of fields such as flexible display, flexible power storage, flexible solar cells, wearable electronics and healthcare monitoring devices. Recently, flexible electronics are being attached on the skin and even implanted into human body to monitor the bio-signals and for treatment purpose. To improve the electrical characteristic and the mechanical properties of flexible electronics, nanoscale fabrications using novel nano-materials are required. Advanced in nanoscale fabrication methods allow construction of the active materials that can combine with the ultra-thin soft substrate to form flexible electronics with high performances and reliability. In this review, wide range of nanoscale fabrication methods for flexible electronics classified in either top-down or bottom-up approaches such as conventional photolithography, soft lithography, nanoimprint lithography, growth, assembly and chemical vapor deposition(CVD) will be reported with specific fabrication processes and results. Here, our aim is to introduce various fabrication methods that can be used to fabricate the flexible electronics.

Our understanding of pull-apart basins and their fault systems has been enhanced by analog experiments and simulations. However, there has been no opportunity to compare the faults that constitute pull-apart basins with surface ruptures during earthquakes. In this study, we investigated the effects of a 2018 earthquake (Mw 7.5) on a pull-apart basin in the Palu-Koro fault system, Sulawesi Island, Indonesia, using geomorphic observations in digital elevation models, optical correlation with pre- and post-earthquake satellite images. A comparison of active fault traces determined by geomorphology with the locations of surface ruptures from the 2018 earthquake shows that some of the boundary faults of the basin are inactive and that active faulting has shifted to basin-shortcut faults and relay ramps. We also report evidence of lateral spreading, in which alluvial fan materials moved around the end of the alluvial fan. These phenomena may provide insights for anticipating the location of future surface ruptures in pull-apart basins.

Lean is one of the systematic approach to achieve higher value for organizations through eliminate non-value-added activities. It is an integrated set of tools, techniques, and principles designed to optimize cost, quality and delivery while improving safety. In Vietnam, industry waste management and treatment has become serious issue. The aim of this research is to present the effective of Lean application for industrial wastes collecting and delivery improvement. Through a case study, this paper showed the way of Lean tools and principles applied for wastes management and treatment such as Value Stream Mapping, Pull system, Visual Control, and Andon.... to get benefit on both economic and environment. In addition, the results introduced a good experience for Vietnamese enterprises in cost saving and sustainable development in waste management.

In this study, we designed a structural model to determine the relationships among push–pull factors, institutional situations, and satisfaction during the COVID-19 pandemic. The 17 selected indicators fell under five domains, namely push factors, pull factors, institutional leadership, international strategies, and satisfaction. Structural equation modeling (SEM) was used to verify the assumptions of the model. Based on 1005 degree-seeking international students' views, this study found that push and pull factors may coincidentally exist, and their functions can be modified by institutional situations. The findings suggest pull factors will, through institutional leadership, impact students' satisfaction, while push factors will not. Moreover, the detection of institutional mediation can provide useful information for specific institutes to develop their future recruiting or retaining strategies. These findings enriched our knowledge of the field during the pandemic. For future studies, this design may be useful to interpret the phenomena of global student mobility in higher education settings.

Several recent epidemiological studies attempted to identify risk factors for Alzheimer's disease. Age, family history, genetic factors (APOE genotype, Down syndrome), physical activity, and a low level of schooling are significant risk factors. In this review, we summarize the known psychosocial risk factors for the development of Alzheimer's disease in Down syndrome patients and their association with neuroanatomical changes in the brains of people with Down syndrome. We completed a comprehensive review of the literature on PubMed, Google Scholar, and Web of Science about psychosocial risk factors for Alzheimer's disease, for Alzheimer's disease in Down syndrome, and Alzheimer's disease in Down syndrome and their association with neuroanatomical changes in the brains of people with Down syndrome. Alzheimer's disease causes early pathological changes in Down syndrome patients, especially in the hippocampus and corpus callosum. The field needs more data about the neuroanatomical changes during childhood, how they change with increasing age, and the presence or absence of psychosocial risk factors. Further neuroimaging and psychosocial assessment-focused research is needed to understand the mechanisms leading to Alzheimer's disease at an early age and create more sensitive and relevant clinical, memory, and reasoning assessments for people with Down syndrome.

T cell function is determined by transcriptional networks that are regulated by epigenetic programming via posttranslational modifications (PTMs) of histone proteins and DNA. Bottom-up mass spectrometry (MS) can identify histone PTMs, whereas intact protein analysis with high-field Fourier transform ion cyclotron resonance MS (FTICR-MS) can detect species missed by bottom-up approaches. We used high-resolution reversed-phase liquid chromatography (RPLC) FTICR-MS, alternating electron transfer dissociation (ETD) and collision-induced dissociation (CID) on precursor ions to maximize fragmentation of uniquely modified species. First online RPLC separation sorted histone families then weak cation exchange hydrophilic interaction liquid chromatography (WCX-HILIC) separated species heavily clad in PTMs. Tentative PTM identifications were assigned by matching peptide masses to predicted theoretical masses that were verified with tandem MS. We used this innovative approach for Histone-intact protein PTM mapping (HiPTMap) and to quantify PTMs on core histones purified from CD8+ T cells directly isolated ex vivo post-influenza infection. Activation significantly reduced PTMs in vivo following influenza infection, histone maps changed as T cells migrated to infections, and T cells responding to secondary heterologous infections had significantly more PTMs enhancing transcriptional activation. Thus, HiPTMap identifies and quantifies PTMs on CD8+ T cell histones and determines their combinations in T cell states.

Field and numerical investigations at Happisburgh, East coast of England, UK, sought to characterize beach thickness and determine geologic framework controls on coastal change. After a major failure of coastal protection infrastructure, removal of about 1 km of coastal defense along the otherwise protected cliffed coastline of Happisburgh triggered a period of rapid erosion over 20 years of ca. 140 m. Previous sensitivity studies suggested that that beach thickness plays a major role in coastal recession. These studies were limited, however, by a lack of beach volume data. In this study, we have integrated the insights gained from our understanding of the Quaternary geology of the area, a novel non-intrusive passive seismic survey method, and a 3D novel representation of the subsurface source and transportable material into a coastal modelling environment to explore the role of beach thickness on the back wearing and down wearing of the cliffs and consolidated platform, respectively. Results show that beach thickness is non-homogeneous along the study site: we estimate that the contribution to nearshore sediment budget via platform down wearing is of a similar order of magnitude as sediment lost from the beach and therefore non-negligible. We have provided a range of evidence to support the idea that the Happisburgh beach is a relatively thin layer perched on a sediment rich platform of sand and gravel. This conceptualization differs from previous publications, which assumes that the platform was mostly till and fine material. This has direct implication on the regional sediment management of along this coastline. The present study contributes to our understanding of a poorly known aspect of coastal sediment budgeting and outlines a quantitative approach that allows for simple integration of geological understanding for coastline evolution assessments worldwide.

Rapid draw-down in an earthfill dam has serious implications for dam safety regarding slope stability. The evaluation of reservoir draw-down impact on slope stability was carried out considering the case study of 8 hours of rapid draw-down of the Middle Marsyangdi Hydroelectric Power Project (MMHPP) rock-fill dam using the Limit Equilibrium Method (LEM) and stress-based Finite Element Method (FEM). The time-dependent factor of safety (FOS) was evaluated and found that the 8 hours of rapid draw-down undertaken in October 2012 for reservoir flushing was unsafe with a draw-down rate of 1.91m/h. The resulting FOS of 1.28 and 1.27 using LEM and FEM was classified as unsafe as per the US Army Corps of Engineers’ guideline, the minimum required factors of safety should be greater than 1.3. The minimum safe allowable draw-down rate of 0.76m/h for 20 hours was identified. Applying three layers of horizontal filter materials and increasing the upstream dam’s permeability provided adequate FOS results for all cases by increasing seepage discharge to reduce the destabilizing excess pore water pressure. Several gradual draw-down rates were also tested and found that FOS increases with decreased draw-down rates, as it reduces the excess pore water pressure controlled with stabilizing existing water load.

The absolute absorption cross section of the ethyl peroxy radical, C2H5O2, in the Ã←X ̃ electronic transition with the peak wavelength at 7596 cm-1, has been determined by the method of dual wavelengths time resolved continuous wave cavity ring down spectroscopy. C2H5O2 radicals were generated from pulsed 351 nm photolysis of C2H6/Cl2 mixture in presence of O2 and detected on one of the CRDS paths. Two methods have been applied for the determination of the C2H5O2 absorption cross section: (i) based on Cl-atoms being converted alternatively to either C2H5O2 by adding C2H6 or to hydro peroxy radicals, HO2, by adding CH3OH to the mixture, whereby HO2 was reliably quantified on the second CRDS path in the 21 vibrational overtone at 6638.2 cm-1 (ii) based on the reaction of C2H5O2 with HO2, measured under either excess HO2 or under excess C2H5O2 concentration. Both methods lead to the same peak absorption cross section of C2H5O2,7596 cm-1 = (1.0±0.2) × 10-20 cm2. The rate constant for the cross reaction between of C2H5O2 and HO2 has been measured to be (6.5±1.6) × 10-12 cm3 molecule-1 s-1.

Disparities between fold amplitude (A) and intrusion thickness (Hsill) are critical in identifying elastic or inelastic deformation in a forced fold. However, accurate measurement of these two parameters is challenging because of the limit in separability and detectability for the seismic data. In the TZ-47 exploring area from the Tarim Basin, Northwest China, we combined wireline data and 3-D seismic data, to accurately constrain the fold amplitude and total thickness of sills that inducing the roof uplift. The measurement results show that the forced fold amplitude is 155 m and the total sill thickness is 148.4 m. When using a magma density of 2.7 g/cm3, and solid rock density of 3 g/cm3, the molten magma thickness at the time of intrusion would be 153.8 m, which is almost no difference from the forced fold amplitude. Therefore, the TZ-47 fold is a pure elastic forced fold induced by emplacement of multiple sills. Measurement solely based on seismic data may not be able to detect some thin interlayers and may result in large errors.

Promoter is a small region of DNA sequence in response to various transcription factors, which initiates a particular gene expression. The promoter-engineered bio-sensor can activate or repress gene expression through transcription factor recognizing specific molecules, such as polyamine, sugars, lactams, amino acids, organic acids or redox molecule, however, the reported applications of promoter enhanced bio-sensor are not too much. This review paper highlights the strategies of construction of promoter-gene engineered bio-sensor with human and bacteria’s genetic promoter array for high-throughput screening (HTS) molecular drugs, study of membrane protein’s localization and nucleocytoplasmic shuttling mechanism of regulating factor, enzyme activity, detection of the toxicity of intermediate chemicals, and probing bacteria density to improve value-added product titer. These bio-sensors’s sensitivity and specificity can be further improved by proposed approaches of Mn²⁺ and Mg²⁺ added random Error-prone PCR and site-directed mutagenesis which is applied for construction of bacteria’s “mutant library”. It is expected to establish flexible HTS platform (Bio-sensor array) to large-scale screen transcription factor-acting drugs, reducing the toxicity of intermediate compounds, and constructing gene dynamic regulatory system in “push and pull” mode to effectively regulate the valuable medicinal product production. This proposed novel promoter-engineered biosensors aided synthetic genetic circuit construction will maximize the efficiency of bio-synthesis of medicinal compound, which will greatly promote the development of microbial metabolic engineering and biomedical science.

AISI 1050 steel circular pocket milling under minimum quantity lubrication (MQL) surroundings including nozzle elevation angle, lubricant flow rate, air pressure and cutting speed was studied. The machined surface quality (Ra) was evaluated for Up-milling side and Down-milling side. In this study, to obtain an manifest explanation on the pivotal effective parameters of MQL surroundings and cutting speed on the machined surface quality (Ra) through analyzing Taguchi L9 (34-2) approach and ANOVA calculation to identify those parameters, by utilizing the experimental outcomes to interpret three-dimensional (3D) surface plots and the diagrams of Signal-to-Noise ratios and major impact plots of Mean. The obtained outcomes of optimal operating parameters indicated that the pivotal effective parameters of MQL surroundings are nozzle elevation angle and lubricant flow rate on the machined surface quality. Simultaneously, a quadratic mathematical paradigm generated by using response surface design (RSD) and desirableness function evaluation were utilized to forecast the optimal values of the machined surface quality compared to Taguchi method. The results unveiled that the optimal values of the machined surface quality are adjacent to experimental attained values. The machined surface quality has been significantly improved using MQL surroundings.

Top-down models are defined by hardware architects to provide information on the utilization of the different hardware components. The target is to isolate the users from the complexity of the hardware architecture while giving them insight into how efficiently the code is using the resources. In this paper, we explore the applicability of 4 top-down models defined for different hardware architectures powering state-of-the-art HPC clusters (Intel Skylake, Fujitsu A64FX, IBM Power9, and Huawei Kunpeng 920) and propose a model for AMD Zen 2. We study a parallel CFD code used for scientific production to compare these 5 Top-Down models. We evaluate the level of insight achieved, the clarity of the information, the ease of use, and the conclusions that each one allows us to reach.

Dog Assisted Therapy is hypothesized to lower stress in children with Autism Spectrum Disorder (ASD) and children with Down Syndrome (DS), which may be visible on a physiological level. In this study, we measured Heart Rate Variability (HRV) and salivary cortisol of 20 children with DS or ASD at the beginning and end of 6 weekly sessions of Dog-Assisted Therapy. We found a decrease of cortisol levels during single sessions, but no overall effect after 6 sessions (6 weeks). The effect of Dog Assisted Therapy on the increase of HRV could not be confirmed. This study is one of the first to use physiological measurements to test the effects of DAT.

Device-mediated, non-invasive drug delivery across the blood-brain barrier (BBB) represents a significant advancement in treating neurological diseases. The BBB is a tightly packed layer of endothelial cells that shields the brain from harmful substances in the blood, allowing necessary nutrients to pass through. It is a highly selective barrier, which poses a challenge to delivering therapeutic agents into the brain. Several non-invasive techniques and devices have been proposed or investigated to enhance drug delivery across the BBB. This paper presents the current state of the art and case studies that address the pharmacology, technology, delivery systems, regulatory approval, ethical concerns, and future possibilities.

This work communicates cavity ring-down spectroscopy (CRDS) of methylidyne (CH) in a chemiluminescent plasma that is produced in a microwave cavity. Of interest are the rotational lines of the 0-0 vibrational transition for the A-X band and the 1-0 vibrational transition for the B-X band. The reported investigations originate from CH-radical research in 1996 that constituted the first case of applying CRDS to the CH radical. The report also includes recent analysis that shows excellent agreement of measured and computed data, and it communicates CH line strength data.

The Asian world is home to a multitude of venomous and dangerous snakes, which are attributed to various medical effects used in the preparation of traditional snake tinctures and alcoholics, like the Japanese snake wine, named Habushu. The aim of this work was to perform the first quantitative proteomic analysis of the Protobothrops flavoviridis pit viper venom. Accordingly, the venom was analyzed by complimentary bottom-up and top-down mass spectrometry techniques. The mass spectrometry-based snake venomics approach revealed that more than half of the venom is composed of different phospholipases A2 (PLA2). The combination with an intact mass profiling led to the identification of the three main Habu PLA2s. Furthermore, nearly one-third of the total venom consists of snake venom metalloproteinases and disintegrins, and several minor represented toxins families were detected: CTL, CRISP, svSP, LAAO, PDE and 5’-nucleotidase. Finally, the venom of P. flavoviridis contains certain bradykinin-potentiating peptides and related peptides, like the svMP inhibitors pEKW, pEQW, pEEW and pENW. In preliminary MTT cytotoxicity assays the highest cancerous-cytotoxicity of the crude venom was measured against human neuroblastoma SH-SY5Y cells and shows in some fractions disintegrin-like effects.

This paper develops mathematical models examining possible roles of oxytocin and oxytocin receptors in the development of autism. This is done by demonstrating that mathematical operations on normalized data from the Stanford study (K.J. Parker, 2016), which establishes a correspondence between severity of autism in children and their oxytocin blood levels, generates a graph that is the same as the graph of mathematical operations on a normalized theoretical model for the severity of autism. This procedure establishes the validity of the theoretical model and the significance of oxytocin receptors in autism. A steady-state model follows, explaining the constant baseline concentrations of oxytocin observed in the cerebral spinal fluid and blood in terms of the neuromodulation by oxytocin of oxytocin receptors on the magnocellular neurons that produce oxytocin in nuclei in the hypothalamus. The implications of these models for possible roles of oxytocin and oxytocin receptors in autism is considered for several unrelated conditions that may be associated with autism. These are: oxytocin receptor desensitization and down-regulation as factors during labor in offspring autism development; reductions in the oxytocin receptor numbers in the fixed oxytocin receptor expression that occurs before birth; MAST Immune System disease; and the excess number of dendritic spines from lack of pruning observed in brains of autistic people. Research into the feasibility of generating magnocellular neurons and other neurons from adult stem cells is suggested as a way of doing invitro studies of oxytocin and oxytocin receptors to assess the validity of theories presented in this paper.

In the paper we show that the general relativity in recent Einstein-Palatini formulation is equivalent to a gauge field. We begin with a bit of information of the Einstein-Palatini formulation and derive Einstein field equations from it. In the next section, we consider general relativity with a positive cosmological constant in terms of the corrected curvature. We show that in terms of the corrected curvature general relativity takes the form typical for a gauge field. Finally, we give a geometrical interpretation of the corrected curvature.

The molecular basis of Down syndrome (DS) predisposition to leukemia is not fully understood but involves various factors such as chromosomal abnormalities, oncogenic mutations, epigenetic alterations, and changes in selection dynamics. Myeloid leukemia associated with DS (ML-DS) is preceded by a preleukemic phase called transient abnormal myelopoiesis driven by GATA1 gene mutations and progresses to ML-DS through additional mutations in cohesin genes, CTCF, RAS, or JAK/STAT pathway genes. DS-related ALL (ALL-DS) differs from non-DS ALL in terms of cytogenetic subgroups and genetic driver events and aberrant expression of CRLF2, JAK2 mutations, and RAS pathway activating mutations are frequent in ALL-DS. Recent advancements in single-cell multi-omics technologies have provided unprecedented insights into the cellular and molecular heterogeneity of DS-associated hematologic neoplasms. Single-cell RNA sequencing and digital spatial profiling enable the identification of rare cell subpopulations, characterization of clonal evolution dynamics, and exploration of the tumor microenvironment's role. These approaches may help identify new druggable targets and tailor therapeutic interventions based on distinct molecular profiles, ultimately improving patient outcomes with the potential to guide personalized medicine approaches and the development of targeted therapies.

As there exist no repulsive forces in strong interaction, in a hypothetical approach, strong interaction can be assumed to be equivalent to a large gravitational coupling. Based on this concept, strong coupling constant can be defined as a ratio of the electromagnetic force and the gravitational force associated with proton, neutron, up quark and down quark. With respect to the product of strong coupling constant and fine structure ratio, we review our recently proposed two semi empirical relations and coefficients 0.00189 and 0.00642 connected with nuclear stability and binding energy. We wish to emphasize that- by classifying nucleons as ‘free nucleons’ and ‘active nucleons’, nuclear binding energy can be fitted with a new class of ‘three term’ formula having one unique energy coefficient. Based on the geometry and quantum nature, currently believed harmonic oscillator and spin orbit magic numbers can be considered as the lower and upper “mass limits” of quark clusters.

Insufficient mixing in large-scale bioreactors, provokes gradient zones of substrate, dissolved oxygen, pH and other parameters. E. coli responds to a high glucose, low oxygen feeding zone with the accumulation of mixed acid fermentation products, especially formate, but also with the synthesis of non-canonical amino acids, such as norvaline, norleucine and -methyl-norleucine. These amino acids can be mis-incorporated into recombinant products, which causes a problem for pharmaceutical production whose solution is not trivial. While these effects can also be observed in scale down bioreactor systems, these are challenging to operate. Especially the high-throughput screening of clone libraries is not easy, as fed-batch cultivations would need to be controlled via repeated glucose pulses with simultaneous oxygen limitation, as has been demonstrated in well controlled robotic systems. Here we show that not only glucose pulses in combination with oxygen limitation can provoke the synthesis of these non-canonical branched-chain amino acids, but also that pyruvate pulses produce the same effect. Therefore we combined the enzyme based glucose delivery method Enbase® in a PALL24 mini-bioreactor system and combined repeated pyruvate pulses with simultaneous reduction of the aeration rate. These cultivation conditions, produced an increase in the non-canonical branched chain amino acids norvaline and norleucine in both the intracellular soluble protein and inclusion body fractions with mini-proinsulin as an example product, and this effect was verified in a 15 L stirred tank bioreactor. To our opinion this cultivation strategy is easy to apply for the screening of strain libraries under standard laboratory conditions if no complex robotic and well controlled parallel cultivation devices are available.

Apraxia of speech is a persistent speech motor disorder that affects speech intelligibility. Studies on speech motor disorders with transcranial Direct Current Stimulation (tDCS) have been mostly directed to post-stroke aphasia. Only a few tDCS studies have focused on apraxia of speech or childhood apraxia of speech (CAS), and no study has investigated individuals with CAS and people with trisomy 21 (T21, Down Syndrome). This study examined the effects of tDCS combined with a motor learning task in developmental apraxia of speech co-existing with T21 (ReBEC RBR-5435x9). The accuracy of speech sound production of nonsense words (NSWs) during Rapid Syllable Transition Training (ReST) under 10 sessions of anodal tDCS (1.5 mA, 25 cm) over the Broca’s area with cathode over the contralateral region was compared to 10 sessions of sham-tDCS and 4 control sessions in a 20-year-old male individual with T21 presenting moderate-severe childhood apraxia of speech (CAS). The accuracy for NSWs production progressively improved (gain 40%) under tDCS only (sham-tDCS and control sessions showed <20% gain). A decrease in speech severity from moderate-severe to mild-moderate indicated transfer effects in speech production. The speech accuracy under tDCS was correlated with Wernicke’s area activation (P3 current source density), which in turn, was correlated with the activation of the left supramarginal gyrus and the Sylvian Parietal Temporal Junction. Repetitive bihemispheric tDCS paired with ReST may have facilitated the speech sound acquisition in a young adult with T21 and CAS, possibly by recruiting brain regions required for the phonological working memory.

Sanitation, water supply and their governance remain major challenges in many Pacific Island Countries. National sustainable development strategies (NSDSs) are promoted throughout the Pacific as overarching improved governance instruments to identify priorities, plan solutions and fulfill commitments to sustainable development. Their relevance to local village-level development priorities is uncertain. The Kingdom of Tonga provides opportunities to compare both. Tonga’s Strategic Development Frameworks (TSDFI 2011-2014 and TSDFII 2015-2025) were developed to focus government and its agencies on national outcomes. From 2007 to 2016, 136 villages throughout Tonga’s five Island Divisions (IDs) formulated Community Development Plans (CDPs) involving separately 80% of women, youth and men in each village. Censuses in 2006 and 2016 show linked improvements in water supply and sanitation systems but reveal IDs with continuing challenges. Sanitation and water are prominent in TSDFI but absent from the current TSDFII. In contrast, CDPs show in one ID, 53% of villages ranked sanitation as a priority with marked differences between IDs and between women, youth and men. CDPs’ sanitation priorities in IDs mostly correspond to sanitation and water metrics in the Censuses, but some reflect impacts of natural disasters. Explanations for differences in sanitation priorities between national and local development plans, as well as suggestions for improving NSDS processes in island countries, are advanced.